Dusp-5 and Snrk-1 coordinately function during vascular development and disease.
Mitogen-activated protein kinases play an integral role in several cellular processes. To regulate mitogen-activated protein kinases, cells express members of a counteracting group of proteins called phosphatases. In this study, we have identified a specific role that one member of this family of phosphatases, dual-specific phosphatase-5 (Dusp-5) plays in vascular development in vivo. We have determined that dusp-5 is expressed in angioblasts and in established vasculature and that it counteracts the function of a serine threonine kinase, Snrk-1, which also plays a functional role in angioblast development. Together, Dusp-5 and Snrk-1 control angioblast populations in the lateral plate mesoderm with Dusp-5 functioning downstream of Snrk-1. Importantly, mutations in dusp-5 and snrk-1 have been identified in affected tissues of patients with vascular anomalies, implicating the Snrk-1-Dusp-5 signaling pathway in human disease.
Pramanik
Kallal
K
Department of Pediatrics, Children's Research Institute Developmental Vascular Biology Program, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Chun
Chang Zoon
CZ
Garnaas
Maija K
MK
Samant
Ganesh V
GV
Li
Keguo
K
Horswill
Mark A
MA
North
Paula E
PE
Ramchandran
Ramani
R
D000818:Animals; D001808:Blood Vessels / Q000196:embryology* / Q000473:pathology; D054637:Dual-Specificity Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006391:Hemangioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008648:Mesoderm / Q000098:blood supply* / Q000196:embryology / Q000473:pathology; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000096:biosynthesis* / Q000235:genetics
D009363:Neoplasm Proteins; D029961:Zebrafish Proteins; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; C442320:DUSP5 protein, human; D054637:Dual-Specificity Phosphatases